This work was carried out with the aim of contributing to the treatment of cancer. Cancer is one of the most common causes of death. It constitutes a public health problem. Photodynamic therapy (PDT) is one treatment ...This work was carried out with the aim of contributing to the treatment of cancer. Cancer is one of the most common causes of death. It constitutes a public health problem. Photodynamic therapy (PDT) is one treatment option. This study contributes to the search for photosensitizing molecules used in PDT. Makaluvamines have shown interesting properties in the treatment of several human cancer cell lines. The present study analyzes the ultraviolet and visible absorption spectroscopic properties of a few Makaluvamines. These have been listed in the literature and can be in neutral or charged states (protonated and methylated). The investigation is based on quantum chemical calculations. Molecular geometries and vibrational frequencies have been calculated at the B3LYP/6-311++G(d,p) level. Absorption properties in the visible and ultraviolet spectral range are measured on optimized structures using time-dependent density functional theory (TD-DFT). The absorption spectra are obtained using the “Chemissian” software. The results of our calculations have allowed us to determine the absorption zones of the molecules studied, the energy gaps of the frontier orbitals, the main transitions associated with the absorption process, and their lifetimes. They have also identified four Makaluvamines (E, G, M, and L) that absorb in the therapeutic domain and may have photosensitizer properties.展开更多
Malaria is a real public health problem. It’s one of the pathologies that mobilize the scientific community. Resistance to existing treatments is the basis for the search for new treatments. Some molecules such as Ma...Malaria is a real public health problem. It’s one of the pathologies that mobilize the scientific community. Resistance to existing treatments is the basis for the search for new treatments. Some molecules such as Manzamenones have shown important antimalarial properties. These molecules belong to the family of atypical fatty acid derivatives. This work presents the relative stabilities, some reactivity properties and the privileged sites of interaction by hydrogen bond of fourteen Manzamenones and two antimalarial drugs: quinine and Artemisinin. These analyses were performed using quantum chemical calculations. We employed the two-layer ONIOM calculation method;namely ONIOM (B3LYP/6-311++G (d, p): AM1) for the fourteen Manzamenones. The geometries of the two antimalarials are calculated at B3LYP/6-311++G (d, p). The electrostatic potential (ESP) calculation of all molecules is done at the B3LYP/6-31++G (d, p) level. The formation processes of the molecules are discussed from the thermodynamic quantities we have calculated. The relative stabilities, the energies of the frontier orbitals, the energy gaps, the dipole moment, etc., are evaluated and discussed. The electrostatic potential at the molecular surface has been used to identify the sites favorable to the formation of hydrogen bonds.展开更多
This work was undertaken to analyze intramolecular and intermolecular interactions of Manzamenones from natural bond orbitals (NBO method). For their use in the treatment of malaria, the results of these molecules are...This work was undertaken to analyze intramolecular and intermolecular interactions of Manzamenones from natural bond orbitals (NBO method). For their use in the treatment of malaria, the results of these molecules are compared to those of Artemisinin and Quinine. Manzamenones are a class of atypical fatty acids. They are isolated from a marine sponge of the genus Plakortis kenyensis. The analysis of intramolecular interactions compares the results of each molecule (Manzamenones, Artemisinin and Quinine) in the non-complexed state with those of its complex with a water molecule. Thus, for the same electron donors (i) and associated acceptors (j), the electron density (ED), stabilization energy E<sup>2</sup> related to the delocalization of i to j, the energies of the NBO orbitals ε<sub>i</sub> and ε<sub>j</sub> of the donor and acceptor, respectively, and element of the Fock matrix F<sub>i,j</sub> are determined and compared. The change in E<sup>2</sup> is used to deduce whether or not the molecule is stabilized after complex formation. These analyses allowed to match each Manzamenone to one of the two antimalarials. The intermolecular interactions were analyzed, for each molecule (Manzamenones, Artemisinin and Quinine), in two complexes. These complexes are obtained with a water molecule on the one hand and with an alanine molecule on the other hand. For these interactions, the electron donor and its electron density, the electron acceptor and its electron density as well as the donor—acceptor stabilization energy have been calculated. The ONIOM 2 method is used to study Manzamenones. Theoretical calculations were done using density functional theory (B3LYP) by combining one of the two function bases 6-31++G(d,p) and 6-31+G(d,p).展开更多
文摘This work was carried out with the aim of contributing to the treatment of cancer. Cancer is one of the most common causes of death. It constitutes a public health problem. Photodynamic therapy (PDT) is one treatment option. This study contributes to the search for photosensitizing molecules used in PDT. Makaluvamines have shown interesting properties in the treatment of several human cancer cell lines. The present study analyzes the ultraviolet and visible absorption spectroscopic properties of a few Makaluvamines. These have been listed in the literature and can be in neutral or charged states (protonated and methylated). The investigation is based on quantum chemical calculations. Molecular geometries and vibrational frequencies have been calculated at the B3LYP/6-311++G(d,p) level. Absorption properties in the visible and ultraviolet spectral range are measured on optimized structures using time-dependent density functional theory (TD-DFT). The absorption spectra are obtained using the “Chemissian” software. The results of our calculations have allowed us to determine the absorption zones of the molecules studied, the energy gaps of the frontier orbitals, the main transitions associated with the absorption process, and their lifetimes. They have also identified four Makaluvamines (E, G, M, and L) that absorb in the therapeutic domain and may have photosensitizer properties.
文摘Malaria is a real public health problem. It’s one of the pathologies that mobilize the scientific community. Resistance to existing treatments is the basis for the search for new treatments. Some molecules such as Manzamenones have shown important antimalarial properties. These molecules belong to the family of atypical fatty acid derivatives. This work presents the relative stabilities, some reactivity properties and the privileged sites of interaction by hydrogen bond of fourteen Manzamenones and two antimalarial drugs: quinine and Artemisinin. These analyses were performed using quantum chemical calculations. We employed the two-layer ONIOM calculation method;namely ONIOM (B3LYP/6-311++G (d, p): AM1) for the fourteen Manzamenones. The geometries of the two antimalarials are calculated at B3LYP/6-311++G (d, p). The electrostatic potential (ESP) calculation of all molecules is done at the B3LYP/6-31++G (d, p) level. The formation processes of the molecules are discussed from the thermodynamic quantities we have calculated. The relative stabilities, the energies of the frontier orbitals, the energy gaps, the dipole moment, etc., are evaluated and discussed. The electrostatic potential at the molecular surface has been used to identify the sites favorable to the formation of hydrogen bonds.
文摘This work was undertaken to analyze intramolecular and intermolecular interactions of Manzamenones from natural bond orbitals (NBO method). For their use in the treatment of malaria, the results of these molecules are compared to those of Artemisinin and Quinine. Manzamenones are a class of atypical fatty acids. They are isolated from a marine sponge of the genus Plakortis kenyensis. The analysis of intramolecular interactions compares the results of each molecule (Manzamenones, Artemisinin and Quinine) in the non-complexed state with those of its complex with a water molecule. Thus, for the same electron donors (i) and associated acceptors (j), the electron density (ED), stabilization energy E<sup>2</sup> related to the delocalization of i to j, the energies of the NBO orbitals ε<sub>i</sub> and ε<sub>j</sub> of the donor and acceptor, respectively, and element of the Fock matrix F<sub>i,j</sub> are determined and compared. The change in E<sup>2</sup> is used to deduce whether or not the molecule is stabilized after complex formation. These analyses allowed to match each Manzamenone to one of the two antimalarials. The intermolecular interactions were analyzed, for each molecule (Manzamenones, Artemisinin and Quinine), in two complexes. These complexes are obtained with a water molecule on the one hand and with an alanine molecule on the other hand. For these interactions, the electron donor and its electron density, the electron acceptor and its electron density as well as the donor—acceptor stabilization energy have been calculated. The ONIOM 2 method is used to study Manzamenones. Theoretical calculations were done using density functional theory (B3LYP) by combining one of the two function bases 6-31++G(d,p) and 6-31+G(d,p).
